XtalPi Submits U.S. FDA IND Application for KQTD-126, a Potential First-in-Class, Gut-Restricted Pan-TRK Inhibitor for Chronic Intestinal Pain

• This milestone marks the first IND submission from XtalPi's proprietary pipeline, recently unveiled in its interim results, validating the company's AI and robotics-driven drug discovery platform and its transition to a clinical-stage organization.
• Preclinical data demonstrate sub-nanomolar potency (< 1 nM) alongside a gut-to-blood exposure ratio exceeding 1,000:1, confining pharmacological activity to the gastrointestinal tract to limit systemic exposure.
• The candidate is the industry's first gut-restricted pan-TRK inhibitor developed for IBS and IBD, targeting a critical therapeutic gap in the long-term management of chronic pain without the neurological liabilities of systemic inhibitors.

BOSTON and SHENZHEN, CHINA, Sept. 24, 2026 /PRNewswire/ -- XtalPi (HKEX: 2228), an AI- and robotics-driven drug and materials discovery company, today announced the submission of an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) for KQTD-126. Developed internally, the candidate is a potential first-in-class gut-restricted pan-tropomyosin receptor kinase (pan-TRK) inhibitor designed to treat chronic intestinal pain associated with irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD).

IBS affects approximately 10%–15% of the global population, while more than 10 million people live with IBD. Chronic abdominal pain is a major burden for patients with IBS and can persist in some patients with IBD even when standard therapies control their underlying inflammation. Despite available treatments, additional options that provide sustained pain relief and are suitable for long-term use remain an unmet clinical need. According to BCC Research, the global IBS and IBD therapeutics market is projected to reach US$52.6 billion by 2030.

KQTD-126 targets the TRK family of receptors (TRKA, TRKB, and TRKC), which directly regulate nerve activity and pain-signal amplification in the gut. While inhibiting these pathways can effectively manages this pain, TRK receptors also operate throughout the central nervous system. Consequently, traditional systemic TRK inhibitors carry a high risk of neurological side effects. A viable chronic pain treatment must therefore confine its activity strictly to the gastrointestinal tract.

Achieving this precise biological profile required navigating a vast chemical space to balance target affinity and kinase selectivity with properties governing tissue distribution. To resolve these competing design objectives, XtalPi leveraged its generative and predictive AI models integrated with its fleet of automated chemistry robots. This closed-loop process of computational design, automated synthesis, empirical screening, and molecular refinement allowed the company to iterate across structural variants and achieve robust gut restriction while preserving strong target activity and selectivity.

In preclinical studies, KQTD-126 achieved pan-TRK inhibition at sub-nanomolar concentrations (IC₅₀ < 1 nM) and maintained high selectivity over other kinases. The candidate also demonstrated a gut tissue-to-blood exposure ratio exceeding 1,000:1. Together, these findings support KQTD-126's development as a locally acting treatment intended to deliver sustained pain relief with a wider therapeutic window.

KQTD-126 is the first program in XtalPi's proprietary pipeline to reach an IND submission since the portfolio was unveiled in the company's recent interim results. As a global scientific utility platform, XtalPi draws on a shared foundation of quantum physics, AI, and robotics to deliver discovery capabilities spanning small molecules, antibodies, peptides, siRNA therapeutics, and molecular glues. This comprehensive infrastructure empowers the company and its partners to pursue high-value targets using the modality best suited to the underlying biology. By advancing internal assets alongside established collaborations, XtalPi maximizes the impact of its technology to resolve complex drug design challenges and deliver transformative therapies for patients worldwide.

About XtalPi

XtalPi Holdings Limited (XtalPi, 2228.HK) was founded in 2015 by three physicists from the Massachusetts Institute of Technology (MIT). It is an innovative R&D platform powered by quantum physics, artificial intelligence, and robotics. By integrating first-principles calculations, AI algorithms, high-performance cloud computing, and standardized automation systems, XtalPi provides digital and intelligent R&D solutions for companies in the pharmaceutical, materials science, agricultural technology, energy, new chemicals, and cosmetics industries.

SOURCE XtalPi Inc.